Combining two checkpoint inhibitors, drugs that remove inhibitory signals and restore the immune system’s ability to fight cancer, may be effective in shrinking melanoma tumors or preventing their growth in some patients who previously received standard therapy, according to new research results from the Johns Hopkins Bloomberg~Kimmel Institute. The study results were presented at American Society of Clinical Oncology (ASCO) 2017 Annual Meeting.

Although currently–available immune checkpoint inhibitors have improved survival for some patients with melanoma or other types of cancer, Johns Hopkins study leader Evan J. Lipson, MD, notes that these therapies are often ineffective. For example, in two recent studies, nivolumab (Opdivo), which targets an immune–inhibiting protein known as PD–1, led to two–year survival in only about 60 percent of patients with advanced melanoma.

In an effort to increase that percentage, Lipson and his colleagues tested whether adding a second, still experimental checkpoint inhibitor, which targets another immune–inhibiting protein known as LAG–3, could be effective in treating patients with advanced melanoma.

Lipson and his collaborators in the U.S. and Europe administered nivolumab and the anti–LAG–3 checkpoint inhibitor every two weeks to patients whose melanomas had progressed during or after previous treatment with at least one immune checkpoint therapy. Among 48 patients, 6 (13 percent) experienced a reduction in tumor size, while tumors from an additional 20 patients (42 percent) stabilized. Median duration of follow–up was 14 weeks.

These results, Lipson says, suggest that some patients for whom standard therapy is ineffective may benefit from this novel combination of immune checkpoint inhibitors, which remove molecular “brakes,” allowing the immune system to launch a more effective anticancer attack.

He adds that ongoing clinical trials at Johns Hopkins and elsewhere are currently testing this drug combination in patients with other types of cancer, or adding a third checkpoint inhibitor to the mix.

“Anti–LAG–3 has demonstrated its importance as a component of combination immune checkpoint inhibitor therapy. We continue to develop these novel regimens in order to safely and effectively unleash the tremendous power of the human immune system for as many cancer patients as possible,” Lipson says.